Central effect of endothelin on neurohormonal responses in conscious rabbits.

It has been shown that endothelin-1 (ET-1) binding sites exist in the central nervous system and that the injection of intracerebroventricular ET-1 induces a pressor response. Therefore, we determined the neurohormonal and cardiovascular responses to intracerebroventricular ET-1 (25 pmol/kg) in conscious rabbits with chronically instrumented electrodes on the renal sympathetic nerve. Intracerebroventricular ET-1 provoked a prompt increase in arterial pressure and in renal sympathetic nerve activity within 5 minutes, and peak values were obtained at 20 and 40 minutes, respectively. Plasma epinephrine and norepinephrine reached peak values at 5-20 minutes. Plasma vasopressin and plasma glucose levels also increased significantly, but plasma osmolality, hematocrit, and serum sodium and potassium concentrations did not show any changes. Arterial blood gas analysis showed respiratory alkalosis. However, pretreatment with intravenous pentolinium (5 mg/kg), a ganglion blocking agent, abolished these neurohormonal and cardiovascular responses. Conversely, the same dose of intravenous ET-1 (25 pmol/kg) as that used in the intracerebroventricular experiment failed to cause any cardiovascular or renal sympathetic nerve responses. These results suggest that intracerebroventricular ET-1 acts in the central nervous system and causes a pressor response mainly through the enhancement of sympathoadrenal outflow.